The goal of the proposed research is to understand the biochemical mechanism by which neutrotransmitters are released when a nerve impulse reaches an axon terminal and to determine how various polypeptide neurotoxins and low molecular weight metabolic inhibitors and other drugs alter this process. We will attempt to identify the Ca2 plus minus dependent and energy-dependent reactions that are involved in transmitter release. The studies will be performed on the following model systems: synaptosomes and synaptic vesicles from rat brain and cultured PC12 cells, a clonal line from a rat pheochromocytoma.